Through political commitment and community mobilization, Uganda has made notable progress in containing HIV prevalence using a variety of prevention approaches including partner reduction, promotion of ABC (Abstinence, Be Faithful, Use Condoms), and openness regarding HIV. However, stable HIV incidence among young people (1-3% per year), increases in HIV risk behaviors, and new concerns about prevention fatigue and behavioral disinhibition have tempered optimism generated by Uganda's prevention successes. Using an innovative combination of quantitative and qualitative methods, as well as a comprehensive theoretical framework for HIV transmission, the Rakai Youth Project (RYP) would first explore the changing patterns of HIV incidence among youth 15-24 years and would assess the influence of social and developmental risk factors for new HIV infections over time. The existing Rakai Community Cohort Study (RCCS) offers a unique opportunity to explore risk factors for HIV infection among youth, providing a longitudinal dataset with a broad array of potential HIV determinants, over 18 years (1994-2012). These include social context, individual psychosocial and social developmental factors, sexual behaviors, and biological factors. We will compare the specifics of HIV risks by marital status and age of partners, by school attendance and achievement, and on the basis of pregnancy intentions and desires. Moreover, the umbrella Rakai Health Sciences Program has a well-developed Qualitative Research Department that allows for the exploration of the nuanced pathways between social and developmental factors and HIV infection---including the influence of HIV prevention programs, adolescent life goals and opportunities, peer pressure, relationship dynamics, and other social influences---that are difficult to fully capture in quantitative questionnaires. A second project aim would explore the specific role of HIV policies and programs in influencing HIV incidence among youth in the Rakai District. The RYP will explore changing HIV risk over four key generations of HIV prevention and care programs in Uganda: the Zero grazing era, the shift to ABC and abstinence education, the post anti-retroviral (ARV) treatment generation, and young people who have come of age after the advent of male circumcision (MC) availability. The new availability of ARVs and MC has raised considerable concerns about behavioral disinhibition among youth. Colleagues from Uganda and the U.S. will work together to synthesize and triangulate these findings. On the basis of the research findings, the RYP will develop recommendations for structural-level and educational interventions for youth in Rakai, Uganda, and elsewhere who are at-risk of HIV infection. Related research dissemination activities will be targeted strategically toward key policy and program leaders at the community, national, and international levels. PUBLIC HEALTH RELEVANCE: The proposed Rakai Youth Project (RYP) would explore the changing patterns of HIV incidence among youth 15-24 years and will assess the influence of social and developmental risk factors for new HIV infections over time. We would use new qualitative data collection and the existing Rakai Community Cohort Study to explore changing risk factors for HIV infection among youth over the period 1994-2012. The RYP would also explore the specific role of HIV policies and programs in influencing HIV incidence among youth in the Rakai District and develop recommendations for structural-level and educational interventions for youth HIV prevention.